Domain wall roughening in dipolar films in the presence of disorder

We derive a low-energy Hamiltonian for the elastic energy of a N\'eel domain wall in a thin film with in-plane magnetization, where we consider the contribution of the long-range dipolar interaction beyond the quadratic approximation. We show that such a Hamiltonian is analogous to the Hamiltonian of a one-dimensional polaron in an external random potential. We use a replica variational method to compute the roughening exponent of the domain wall for the case of two-dimensional dipolar interactions.Comment: REVTEX, 35 pages, 2 figures. The text suffered minor changes and references 1,2 and 12 were added to conform with the referee's repor

Metal-Protein Complex-Mediated Transport and Delivery of Ni²⁺ to TCR/MHC Contact Sites in Nickel-Specific Human T Cell Activation

Nickel allergy clearly involves the activation of HLA-restricted, skin-homing, Ni-specific T cells by professional APCs. Nevertheless, knowledge concerning the molecular details of metal-protein interactions underlying the transport and delivery of metal ions to APC during the early sensitization phase and their interactions with HLA and TCRs is still fragmentary. This study investigates the role of human serum albumin (HSA), a known shuttling molecule for Ni2+ and an often-disregarded, major component of skin, in these processes. We show that Ni-saturated HSA complexes (HSA-Ni) induce and activate Ni-specific human T cells as potently as Ni salt solutions when present at equimolar concentrations classically used for in vitro T cell stimulation. However, neither HSA itself nor its Ni-binding N-terminal peptide are involved in determining the specificity of antigenic determinants. In fact, HSA could be replaced by xenogeneic albumins exhibiting sufficient affinity for Ni2+ as determined by surface plasmon resonance (Biacore technology) or atomic absorption spectroscopy. Moreover, despite rapid internalization of HSA-Ni by APC, it was not processed into HLA-associated epitopes recognizable by Ni-specific T cells. In contrast, the presence of HSA-Ni in the vicinity of transient contacts between TCR and APC-exposed HLA molecules appeared to facilitate a specific transfer of Ni2+ from HSA to high-affinity coordination sites created at the TCR/HLA-interface

Assurance for Endurance? Introducing a Novel Ergonomics Curriculum to Reduce Pain and Enhance Physical Well-Being Among GI Fellows

Musculoskeletal pain and injuries (MSKPI) are common among gastroenterologists (GI) and GI fellows. Common areas of pain include the back, neck, hands/fingers, shoulders, and elbows. Although the prevalence of career-related pain and injuries among GIs is high, few endoscopists receive training in how to prevent MSKPI. We developed an ergonomics curriculum for our GI fellows that consisted of two modules that were led by physical therapists. Twelve out of 15 GI fellows, and one out of two hepatology fellows, participated in Module 1. Prior to the first module, 77% of participants reported pain in one or more body parts. Of those who reported pain, 100% of the fellows stated that this pain occurred during procedures, and 50% indicated this pain was performance-limiting. After completing Module 1, 100% of fellows reported that this was a valuable topic and 100% of the participants felt that this information would both help them feel and perform better. All fellows stated they had an immediate decrease in physical discomfort after engaging in the exercises that were included in Module 1. Eight fellows participated in Module 2. At the end of this module, 100% of fellows reported that this ergonomics training would likely help them to "physically perform better during procedures" and 100% of fellows indicated a reduction of physical discomfort (pain, aching) immediately after completing these exercises. Preliminary data indicated that this novel curriculum was perceived as valuable by GI fellows and that practicing these exercises reduced pain, particularly in the neck and the lower back

HIV-1 Antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor

SummaryMammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection